近日，瑞典卡罗林斯卡大学教授Niklas K. Björkström小组的最新研究探明了短暂的组织驻留和淋巴输出定义了人类CD56bright NK细胞的稳态。相关论文于2025年10月14日发表在《自然—免疫学》杂志上。

在这里，研究团队采用了一种综合的方法，采用动态的人、人源化的动物和非人灵长类动物模型，并对传出淋巴液进行采样，以确定人类NK细胞的再循环和TR模式。通过血管内标记，该研究团队发现CD56bright NK细胞在稳定状态下进入组织壁龛。

此外，在人肝移植中，供体来源的CD56bright NK细胞在移植后早期代表了主要的TR NK细胞群，但随着时间的推移，被浸润的受体NK细胞所取代，这些NK细胞建立了TR特征，这一过程部分由Runx3调节。瞬时TR CD56亮NK细胞通过淋巴循环，在引流淋巴结和传出淋巴液中显示一致的表型，在淋巴结出口阻断时从外周血中减弱。最后，CD56dim NK细胞在稳定状态下被限制在脉管系统中，在炎症发生时进入淋巴结。本研究为人类NK细胞群的短暂组织驻留和再循环模式提供了一个机制框架。

据介绍，人类组织驻留（TR） CD56bright自然杀伤（NK）细胞可以通过从小鼠研究中推断的整合素和趋化因子受体的表达来识别，但其稳态的许多方面尚不清楚。

附：英文原文

Title: Transient tissue residency and lymphatic egress define human CD56bright NK cell homeostasis

Author: Niehrs, Annika, Hertwig, Laura, Buggert, Marcus, Nordstrm, Isabella, Statzu, Maura, Pampena, M. Betina, Samer, Sadia, Knox, James J., Strunz, Benedikt, Sun, Dan, Nguyen, Son, Janoschka, Claudia, Xing, Yafei, Wu, Vincent H., Sparrelid, Ernesto, Alisjahbana, Arlisa, Gao, Yu, Sleiers, Natalie, Strauss, Otto, Filipovic, Iva, Ponzetta, Andrea, Medina-Andrade, Itzel, Nilsn, Vera, Jorns, Carl, Cornillet, Martin, Maucourant, Christopher, Ziegenhain, Christoph, Hengst, Julia, Tweet, George, Kroll, Kyle, Golden, Gregory J., Wedemeyer, Heiner, Krtnc, Murat, Dori, Yoav, Itkin, Maxim G., Klotz, Luisa, Schaffer, Marie, Ericzon, Bo-Gran, Ivarsson, Martin A., Paiardini, Mirko, Nowak, Greg, Willinger, Tim, Reeves, R. Keith, Betts, Michael R., Bjrkstrm, Niklas K.

Issue&Volume: 2025-10-14

Abstract: Human tissue-resident (TR) CD56bright natural killer (NK) cells can be identified by expression of integrins and chemokine receptors inferred from murine studies, but many aspects of their homeostasis are unclear. Here we used an integrated approach of dynamic human, humanized mouse and non-human primate models and sampling of efferent lymph fluid to determine recirculation and TR patterns of human NK cells. By intravascular labeling, we showed that CD56bright NK cells access tissue niches at steady state. Furthermore, in human liver transplantation, donor-derived CD56bright NK cells represent the dominant TR NK cell population early after transplantation, but are replaced over time by infiltrating recipient NK cells that establish TR traits, a process partly regulated by Runx3. Transient TR CD56bright NK cells recirculated via lymphatics, displaying a consistent phenotype detectable in draining lymph nodes and efferent lymph fluid, and waned from peripheral blood on lymph node egress blockade. Finally, CD56dim NK cells, constrained to vasculature at steady state, entered lymph nodes upon inflammation. This study provides a mechanistic framework for the transient tissue residency and recirculation pattern of human NK cell populations.

DOI: 10.1038/s41590-025-02290-9

Source: https://www.nature.com/articles/s41590-025-02290-9